miR-17-3p promotes the proliferation of multiple myeloma cells by downregulating P21 expression through LMLN inhibition

被引:19
|
作者
Xiang, Pu [1 ,2 ]
Yeung, Yiu To [3 ]
Wang, Jiheng [4 ,5 ]
Wu, Qiong [3 ,6 ]
Du, Ruijuan [3 ,6 ]
Huang, Chuntian [3 ,6 ]
Jia, Xuechao [3 ,6 ]
Gao, Yunfeng [3 ]
Zhi, Yafei [3 ,6 ]
Guo, Fangqin [6 ]
Wei, Huifang [3 ,6 ]
Zhang, Dandan [3 ]
Liu, Yuzhang [1 ,2 ]
Liu, Lina [1 ,2 ]
Liang, Lijie [1 ,2 ]
Wang, Juan [1 ,2 ]
Song, Yongping [1 ,2 ]
Liu, Kangdong [3 ,6 ,7 ]
Fang, Baijun [1 ,2 ]
机构
[1] Zhengzhou Univ, Affiliated Canc Hosp, Dept Hematol, Zhengzhou 450008, Henan, Peoples R China
[2] Henan Canc Hosp, Henan Hematol Inst, Zhengzhou 450008, Henan, Peoples R China
[3] China US Henan Hormel Canc Inst, Zhengzhou 450001, Henan, Peoples R China
[4] Zhengzhou Univ, Affiliated Canc Hosp, Dept Head & Neck Thyroid, Zhengzhou, Henan, Peoples R China
[5] Henan Canc Hosp, Zhengzhou, Henan, Peoples R China
[6] Zhengzhou Univ, Sch Basic Med Sci, Dept Pathophysiol, Zhengzhou 450001, Henan, Peoples R China
[7] Canc Chemoprevent Int Collaborat Lab, Zhengzhou 450001, Henan, Peoples R China
基金
中国国家自然科学基金;
关键词
LMLN; miR‐ 17‐ 3p; multiple myeloma; p21; plasma biomarker;
D O I
10.1002/ijc.33528
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Multiple myeloma (MM), a hematological malignancy, has a poor prognosis and requires an invasive procedure. Reports have implicated miRNAs in the diagnosis, treatment and prognosis of hematological malignancies. In our study, we evaluated the expression profiles of miR-17-3p in plasma and bone marrow mononuclear cells of monoclonal gammopathy of undetermined significance (MGUS) and MM patients and healthy subjects. The results showed that the plasma and mononuclear cell expression levels of miR-17-3p in MM patients were higher than those in MGUS patients and normal controls. In addition, the expression of miR-17-3p was positively correlated with diagnostic indexes, such as marrow plasma cell abundance and serum M protein level, and positively correlated with the International Staging System stage of the disease. Receiver operating characteristic curve analysis suggested that miR-17-3p might be a diagnostic index of MM. Moreover, miR-17-3p regulated cell proliferation, apoptosis and the cell cycle through P21 in MM cell lines and promoted MM tumor growth in vivo. Furthermore, we predicted and verified LMLN as a functional downstream target gene of miR-17-3p. Negatively regulated by miR-17-3p, LMLN inhibits MM cell growth, exerting a tumor suppressive function through P21. Taken together, our data identify miR-17-3p as a promising diagnostic biomarker for MM in the clinic and unveil a new miR-17-3p-LMLN-P21 axis in MM progression.
引用
收藏
页码:3071 / 3085
页数:15
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